The study, “Deterioration in Clinical Status Is Not Enough to Suspend Eculizumab: A Genetic Complement-Mediated Atypical Hemolytic Uremic Syndrome Case Report,” was published in the journal Case Reports in Nephrology.
Soliris is an engineered antibody developed and marketed by Alexion that works by specifically targeting the complement C5 protein, chronically activated in people with aHUS. The complement system is a set of over 20 blood proteins that form part of the body’s immune defenses.
This therapy has been approved to treat aHUS in the United States, Japan, and several countries in Europe. Currently recommended as a first-line treatment, the medicine is administered directly into the bloodstream, and involves a first induction phase followed by lifetime maintenance in biweekly doses.
Italian researchers reported the case of a woman, age 51, who was referred to the hospital with an acute episode of high blood pressure and acute kidney injury.
She had been previously diagnosed with chronic kidney disease of unknown cause, reaching end-stage renal disease at age 19. At this point she underwent a kidney transplant and started taking immunomodulatory medicines to prevent organ rejection.
However, 18 years later she started to show signs of renal damage, with very high blood levels of the biomarker creatinine (707.36 𝜇mol/L; normal values 44-88 𝜇mol/L).
Although no signs of organ rejection or infections were found in a kidney biopsy, the patient started on immunosuppressive treatment with tacrolimus and prednisone, which gradually resolved her kidney injury symptoms and lowered creatinine levels.
Yet, three weeks later she was referred to the emergency room with another acute episode of high blood pressure and pulmonary edema (fluid accumulation).
Laboratory analysis revealed a pattern of hemolysis (red blood cells destruction), including high levels of bilirubin, low platelet counts, and severe anemia.
Treatment with tacrolimus was stopped, and doses of CellCept (mycophenolate mofetil) and prednisone were increased. However, no response was observed.
Based on these findings consistent with aHUS, the patient started taking 900 mgs of Soliris after a short course of antibiotic prophylaxis to prevent potential infections. Despite a good initial response, her renal function started to deteriorate, requiring hemodialysis.
Following a brief clinical improvement and increased levels of platelets, she started responding poorly to Soliris, also experiencing fever, seizures, brain hemorrhage, and shortness of breath.
After a period with regular dialysis sessions, the clinical team decided to stop Soliris therapy due to significant clinical deterioration, although the initial Soliris induction therapy had not been completed.
She was discharged from the hospital after showing progressive improvement. However, a new blood analysis showed that aHUS manifestations had only been partially resolved.
Genetic testing confirmed two mutations in genes previously linked to aHUS — THBD and CFI — confirming diagnosis. Mutations in these genes have not been proposed as causing aHUS, but rather as risk factors for its development.
Treatment with Soliris (1,200 mg every two weeks) was restarted to prevent a relapse. This time, she showed a clear clinical improvement and stopped being dependent on dialysis. Still, based on blood analysis, the team noted that she never achieved a complete response to therapy.
“For the first time, we report an aHUS case in which a peculiar combination of mutations in CFI and THBD is found,” the researchers stated, adding that the initial hypertensive peak may have triggered aHUS.
“Although the clinical scenario could affect the compliance to [Soliris] therapy as well as the risk for … infection,” the final clinical response to therapy restart “seems to advocate that [Soliris] should not be suspended despite a deterioration of clinical conditions,” they added.
“In order to provide reliable risk stratification tools and individualize treatment, the development of biomarkers to monitor [Soliris] response is mandatory in the future,” the investigators said.